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Natural genetic variation in wild-derived mice controls host survival and transcriptional responses during endotoxic shock

GSE272206 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2024/12/31 Platform GPL18480
At a glance

RNA-seq (gene expression) · mouse · 24 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
24 samples: 6 conditions, mostly with about 4 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Natural genetic variation in wild-derived mice controls host survival and transcriptional responses during endotoxic shockImmunoHorizons · 2025
Summary (written by the submitters)
Innate immune cells sense microbial danger signals such as bacterial lipopolysaccharide (LPS) through pattern recognition receptors, resulting in dynamic transcriptional reprogramming and rapid inflammatory responses. If not properly regulated, such responses can be detrimental to the host, as is seen in septic shock. A better understanding of the genetic regulation of transcriptional responses during endotoxemia could provide potential therapeutic insights.
Read the full summary ↓
However, the majority of animal model studies have been performed using classic inbred laboratory strains of mice, typically C57BL/6 (B6), capturing limited genetic diversity and representing a potential blind spot. Here, we compared classic inbred B6 mice with wild-derived and genetically divergent PWD/PhJ (PWD) mice using in vivo and in vitro models of endotoxemia, to determine the role of natural genetic variation in septic shock. Compared with B6 mice, PWD mice were markedly resistant to LPS-induced endotoxic shock. Using LPS stimulation of bone marrow derived dendritic cells (BMDC) and RNA sequencing, we demonstrate that B6 and PWD BMDCs exhibit partially overlapping, yet highly divergent transcriptional responses, with B6 skewed towards stereotypical proinflammatory pathway activation, and PWD engaging regulatory or developmental pathways. To dissect genetic regulation of inflammatory responses by allelic variants, we used BMDCs from a sub-consomic strain carrying a ~50 Mb PWD-derived portion of chromosome 11 on a B6 background. This identified a subset of cis regulated and a large number of trans regulated genes. Bioinformatic analyses identified candidate trans regulators encoded in the chromosome 11 locus as transcription factors Irf1, Ncor1, and Srebf1. Taken together, our results demonstrate that natural genetic variation exerts a pronounced effect on host survival and transcriptional reprogramming during endotoxemia, suggesting possibilities for prediction of sepsis risk and/or personalized therapeutic interventions.
Published in
Natural genetic variation in wild-derived mice controls host survival and transcriptional responses during endotoxic shock
Sabikunnahar B, Snyder JP, Rodriguez PD et al. · ImmunoHorizons 2025 · PMID 40139977 · doi:10.1093/immhor/vlaf007
This dataset
Open GSE272206 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE272206_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1135691 and SRA study SRP519791. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40139977) ↗
Study design
6 conditions, mostly with about 4 replicates each
B6_LPS ×4 B6_Untreated ×4 C57_LPS ×4 C57_Untreated ×4 PWD_LPS ×4 PWD_Untreated ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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